Agents that specifically bind to an opioid receptor in a conformationally specific way can be used to induce a conformational change in the receptor. Such agents have therapeutic applications and can be used in X-ray crystallography studies of the receptor. Such agents can also be used to improve drug discovery via compound screening and/or structure-based drug design.

The present invention relates to compositions and methods for characterizing, diagnosing, and treating cancer. In particular the invention provides the means and methods for the diagnosis, characterization, prognosis and treatment of cancer and specifically targeting cancer stem cells. The present invention provides an antibody that specifically binds to a non-ligand binding membrane proximal region of the extracellular domain of a human Notch receptor and inhibits tumor growth. The present invention further provides a method of treating cancer, the method comprising administering a therapeutically effective amount of an antibody that specifically binds to a non-ligand binding membrane proximal region of the extracellular domain of a human Notch receptor protein and inhibits tumor growth.

The present invention relates to VEGF-binding agents, DLL4-binding agents, VEGF/DLL4 bispecific binding agents, and methods of using the agents for treating diseases such as cancer. The present invention provides antibodies that specifically bind human VEGF, antibodies that specifically bind human DLL4, and bispecific antibodies that specifically bind human VEGF and/or human DLL4. The present invention further provides methods of using the agents to inhibit tumor growth. Also described are methods of treating cancer comprising administering a therapeutically effect amount of an agent or antibody of the present invention to a patient having a tumor or cancer.

Provided in some embodiments are antibodies comprising a heavy chain having no native interchain cysteine amino acids, a light chain having no native interchain cysteine amino acids, and having no native interchain disulphide linkages between the heavy chain and the light chain. Also provided in certain embodiments are antibodies comprising a heavy chain having no native interchain cysteine amino acids, a light chain having no native interchain cysteine amino acids, and having no native interchain disulphide linkages between the heavy chain and the light chain where the native interchain cysteine amino acids have been replaced by amino acids having no thiol moiety.

The invention provides compositions and methods for treating leukemia, for example, acute myeloid leukemia (AML) and B-cell acute lymphoid leukemia (B-ALL). The invention also relates to at least one chimeric antigen receptor (CAR) specific to CD123, vectors comprising the same, and recombinant T cells comprising the CD123 CAR. The invention also includes methods of administering a genetically modified T cell expressing a CAR that comprises a CD123 binding domain. The invention also includes methods of bone marrow ablation for use in treatments necessitating bone marrow reconditioning or transplant.

The present disclosure provides compositions and methods of use involving binding proteins, e.g., antibodies and antigen-binding fragments thereof, that bind to the matrix metalloproteinase-9 (MMP9) protein (MMP9 is also known as gelatinase-B), such as where the binding proteins comprise an immunoglobulin (Ig) heavy chain (or functional fragment thereof) and an Ig light chain (or functional fragment thereof).

Provided herein are methods of treatment to regenerate, restore or rejuvenate a tissue. Methods include making adult somatic and germ cells pluripotent for administration to a patient. Alternatively, created pluripotent cells may be differentiated to the desired tissue type and administered to a patient to repair or enhance the target tissue.

A recombinant vector comprises simian adenovirus 36, simian adenovirus 42.1, simian adenovirus 42.2 and/or simian adenovirus 44 sequences and a heterologous gene under the control of regulatory sequences. A cell line which expresses one or more simian adenovirus-36, -42.1, -42.2 or -44 gene(s) is also described. Methods of using the vectors and cell lines are provided.

Materials and methods for treating and preventing American Foulbrood disease in honeybees, such as materials and methods for using phage lysin enzymes to lyse Paenibacillus larvae, are provided herein.

The present invention relates to the use of the miRNA expression profile, particularly of miR-199a-5p, and the target genes regulated thereby for the diagnosis, prognosis and use of miR-199a-5p inhibitors for treating fibroproliferative disorders.

The invention relates to polynucleotide agents targeting the complement component C5 gene, and methods of using such polynucleotide agents to inhibit expression of C5 and to treat subjects having a complement component C5-associated disease, e.g., paroxysmal nocturnal hemoglobinuria.

In one aspect, the invention relates to a method of loading exosomes with oligonucleotide cargo, by incubating an oligonucleotide comprising one or more hydrophobic modifications with a population of exosomes for a period of time sufficient to allow loading of the exosomes with the oligonucleotide. Exosomes loaded with hydrophobic ally modified oligonucleotide cargo, and uses thereof, are also provided.

Fibrous structures that exhibit a novel combination of properties and to methods for making such fibrous structures are provided.

The invention provides for a proteomic approach for identification of specific bacterial protein profiles that may be used in the development of methods for the diagnosis of bacterial chronic sinusitis. The invention provides for methods for determining the presence of pathogenic bacteria in the upper respiratory tract of a subject using protein profiles of the pathogenic bacteria. The invention also provides for methods of diagnosing a bacterial infection of the upper respiratory tract of a subject using protein profiles of a pathogenic bacteria. In addition, the invention provides for devices, immunoassays and kits for identifying pathogenic bacteria in the upper respiratory tract.

Described herein are methods and compositions for treatment of immune-related diseases or disorders by modulating DD1α activity, alone or in combination with modulation of PD-1 activity. In some embodiments, the methods and compositions described herein are directed to treatment of cancer and/or infections (e.g., bacterial infection, and/or fungal infection). In some embodiments, the methods and compositions described herein are directed to treatment of autoimmune diseases and/or inflammation. In some embodiments, the methods and compositions described herein are directed to treatment of asthma, and allergy. Methods for identifying patients who are more likely to be responsive to and benefit from an immunotherapy that targets DD1α and/or PD-1 activity or expression are also described herein.

The present invention provides methods for assessing whether a subject is at risk of developing a neurological disorder, diagnosing or confirming whether a subject is afflicted with a neurological disorder, assessing whether PD has progressed in a subject afflicted with PD, assessing whether a neurological disorder is developing in a subject who has been identified as being at risk of developing the neurological disorder, assessing whether a subject afflicted with a neurological disorder is likely to benefit from a therapy, assessing whether a subject afflicted with a neurological disorder has benefited from a therapy, treating a subject afflicted with a neurological disorder, and prophylactically treating a subject who has been identified as being at risk of developing a neurological disorder. The present invention also provides epitopes, compounds and compositions relating to these methods.

A cold rolling mill is described wherein the unstressed shape of metal sheet is continuously sensed during rolling by a plurality of negligible displacement force sensors perpendicularly disposed relative to the pass line at a mill location producing a tensile stress above 4,000 p.s.i. in the metal sheet being rolled. The output signals from those sensors underlying opposite edges of the metal sheet are compared to equalize reduction at the sheet edges while the difference between the force measured by a centrally situated sensor and the average force measured by the sensors underlying opposite edges of the sheet provide a signal indicative of the roll bending force required to produce flat sheet.

A button assembly apparatus including a die assembly having two die members movable between an open and closed position. The die members include means for applying a covering on a button shell upon closing of the die members. Upon closing the die members a second time, selectively positionable means render the die members suitable for assembling the covered shell to a body member to complete the button.

Portions of a pin-on button are cut and assembled as a result of a plurality of operations in a machine having a vertical press. Cutter and work deforming tools are displaced by a single press ram to cut blanks and deform the blanks onto a button top placed in one of two die assemblies positioned in alignment below the work deforming tool on the lower end of the ram.

Apparatus for the manufacture of a laminated button comprising a metallic backing plate having a transverse peripheral edge and an outwardly extending flange, an illustrated paper sheet and a protective acetate covering. The apparatus comprises a pneumatically operated press which receives the plate, illustrated sheet and covering, and, with a single downward movement, causes the sheet to conform to the plate and be crimped between the transverse edge and flange.

Apparatus for covering buttons operable in an automatic, semi-automatic or manual mode. The apparatus includes a rotatable table having alternately positioned shell and back receiving lower dies, means for automatically delivering the shells and backs to their respective lower dies, a reciprocating upper die synchronized for movement with the rotation of the rotatable table and engageable with the lower dies at a first station to transfer a shell and fabric covering from a shell receiving lower die to the upper die and press-fit a back from a back receiving lower die into the covered shell in the upper die to form an assembled covered button and having means permitting its use with a range of fabric cover thicknesses, and means for ejecting the assembled covered buttons.

Pigmented substantially crack-free casein plastic compositions containing a minor, luster-imparting quantity of coated mica platelets, wherein at least 75% of the pigment particles possess an average platelet size of below 10 μm., a thickness of about 0.1 to 0.7 μm. and a ratio of diameter to thickness of about 10 to 200.

Apparatus for assembling covered buttons in which a first die assembly including a first punch carrying a first sleeve which sequentially receives a piece of covering material and the button shell with its flange extending toward the open end of the sleeve. A second assembly including a second sleeve having a bore one end of which is formed with a first cam surface extending axially inwardly of the above. The second sleeve is spring loaded to an extended position on a supporting post having a centrally located button back fastener receiving cavity in the end thereof with a second cam surface extending inwardly from the outer edge of the end to the bottom of a recess surrounding the cavity. An annular boss at the inner edge of the recess around the cavity is elevated to allow the material and the shell flange to curl inwardly under the button back. In the retracted position of the second sleeve on the post, the second cam surface forms a continuation of the first. In operation, when the first assembly carrying the covering piece and the shell moves toward the second assembly, the first sleeve stops against the spring loaded bottom sleeve and the punch continues forcing the material down so that the material is tucked inward by the beveled or curved surface of the second sleeve. Upon continued relative movement of the assemblies, the shell flange acts on the cam surface of the second sleeve to force the sleeve to its retracted position and the shell flange is moved inwardly of the back wall under the continued action of the first post, the extent of the inward movement of the shell flange being determined by the thickness of the material of the covering piece, as well as the height of the shell and the type of back used.

A universal assembly machine manufactures conventional buttons with formed backs. The machine comprises a rotatably indexable die table to which are mounted pickup and crimp dies. The die table indexes about a center column of the machine frame. A ram die is advancable and retractable in a pickup stroke and a crimp stroke by means of a handle. The ram die includes a ram outer ring that is rotatable by means of a shifter post joined to the die table. Indexing the die table causes the shifter post to rotate the ram outer ring into a pickup mode or a crimp mode to suit the ram pickup and crimp strokes, respectively. The universal assembly machine also manufactures buttons with flat backs by using a different crimp die pedestal than is used with the formed backs. An adapter on the crimp die pedestal used with formed backs allows that crimp die pedestal to also be used for manufacturing buttons with flat backs. The invention also embraces button medallions. A flat back button is loaded into the pickup die, and the die table is indexed. The ram die is advanced in a third press to form the shell frusto-conical wall of the flat back button inwardly to be flat and parallel to the flat back.

A button system and method of manufacturing the same are provided for identifying fiber from which an article of apparel is manufactured. Initially, an article of apparel manufactured with a predetermined fiber is identified. Next, indicia indicative of the predetermined fiber is selected. Next, at least one button is manufactured with the indicia thereon for identifying the fiber from which the article of apparel is manufactured.

A method for forming a multi-colored cap part of a snap button including the steps of forming a design portion of the cap part of snap button using a first group of molds, which includes a first female mold, a first male mold, and a plate-shaped middle mold, and a slide-plate mold adapted to movably assembled to the first male mold and having a plurality of mold cavities for forming the design portion; removing the slide-plate mold having the design portion molded therein from the first male mold; movably positioning the slide-plate mold into a second female mold included in a second group of molds for forming a body portion of the cap part of snap button; positioning a post for the cap part of snap button in a second male mold of the second group of molds; and forming the body portion.

The present invention relates to a plant-based wrapping paper for wrapping food. The plants (raw materials) may be fruits, herbs, medicinal plants, tea, vegetables and/or spices. The invention further relates to a method for producing said wrapping paper, its use for wrapping food or its use as packaging material.

The present invention is directed to novel organoleptic compounds, a process of augmenting, enhancing or imparting taste to a material selected from the group consisting of a foodstuff, a chewing gum, a dental product, an oral hygiene product and a medicinal product comprising the step of incorporating an olfactory acceptable amount of such novel organoleptic compounds, and a process of improving, enhancing or modifying a fragrance composition through the addition of an olfactory acceptable amount of such novel organoleptic compounds.

A measurement apparatus and method for in-situ quantitative texture measurement of a food snack. The apparatus includes an acoustic capturing device and a data processing unit. The physical interaction in the mouth with saliva, when a human being eats/drinks a food snack, sends pressure waves that propagate through the ear bone and produce an acoustic signal. The acoustic capturing device records and forwards the signal to a data processing unit. The data processing unit further comprises a digital signal processing module that smoothens, transforms and filters the received acoustic signal. A statistical processing module further filters the acoustic signal from the data processing unit and generates a quantitative acoustic model for texture attributes such as hardness and fracturability. The quantitative model is correlated with a qualitative texture measurement from a descriptive expert panel. Another method includes a food snack fingerprinting using an in-situ quantitative food property measurement.

An apparatus for producing a food product is disclosed. The apparatus comprises: an enclosed vessel for holding the food product, the vessel having a first end wall, a second end wall opposite to the first end wall, and a side wall between the first and second end walls; a first agitator rotatably mounted to the first end wall, the first agitator extending inside the vessel towards the second end wall; and a second agitator rotatably mounted to the second end wall, the second agitator extending inside the vessel towards the first end wall. The first agitator is unsupported by the second end wall, and the second agitator is unsupported by the first end wall.

The present invention provides a wafer product decorating apparatus comprising a laser, a collimator, at least one galvanometer driven mirror, and an aspheric scan lens, the apparatus being positionable relative to the wafer product to be decorated wherein the apparatus is configured to provide a laser beam having a spot size of from 100 to 750 μm in diameter on the surface of the product to be decorated and a substantially flat focal plane, characterised in that the focal plane has a depth of field of from 5 mm to 20 mm and that the focal plane of the laser beam is from 5 mm to 30 mm above or below the surface of the product to be decorated. The invention also provides a process for decorating a wafer product.

This disclosure describes a simple, low cost method to produce a modular dry mix that can easily be modified and customized to produce a wide range of easy to aerate, no ice cream machine needed, ice cream and frozen dairy and non-dairy desserts and products made by this process. The method relies on successive simultaneous particle size reduction and blending steps without the use of traditional mix drying operations. The formulations produced by this process are modular and allow quick and simple ingredient substitutions to create distinct finished products. The process yields mixes that produce stronger, more stable foams that don't leave an oily mouth feel. The disclosure also includes a formulation and process used to make ice cream, and related frozen dairy and non-dairy desserts at room temperature in one step where the ingredients do not need to be aged, or homogenized, and aeration occurs without the need for simultaneous cooling or freezing. The process allows the end-user to control and vary the texture, freezing rate, melting point and eating qualities of the product without the use of traditional, home or industrial ice cream machines and a product made by this process. A product produced from this mix consists of a (protein-concentrate and emulsifier)—stabilized, protein-based foam created by combining a powder mix with one or a combination of a large range of above freezing temp liquids then immediately whisking the mixture at room temp to a target overrun without pre-aging, and then freezing that product statically till desired hardness is achieved. The main execution of this process involves the use of dry powders that are transported and sold dry and then reconstituted by the end user before they are combined without pre-treatment, freezing homogenization or aging. The manufacturing process offers significant advantages over current dry mix production methods which require significant upfront investment and produce hard to customize mixes. The formulation and finished product making portions of the invention offer significant improvement over existing manufacturing methods for frozen desserts and dessert mixes that require simultaneous freezing and aeration in terms of cost, convenience, customizability, shelf-stability and environmental impact.

An apparatus for heating foods comprises a supporting structure, a treatment zone designed to receive at least one food product to be heated, a radio frequency dielectric heating system, a system for moderating the temperature of at least one surface of the food product during heating. The temperature moderating system comprises at least one fluid container intended to be interposed between an electrode of the dielectric heating system and a surface of the food product received in the treatment zone. During use of the apparatus, the radio frequency dielectric heating system supplies energy to the food product in the treatment zone, the at least one fluid container receives thermal energy from the surface of the food product, a fluid circulates in the at least one fluid container between the infeed and the outfeed for removing at least part of the thermal energy received.

A brewing system includes a brewing apparatus and a capsule containing a substance for brewing. The capsule has an opening on one side and a base on an opposite side. The base includes a light input surface, a light-output surface and a light conductor to conduct light from the light input surface to the light output surface. The apparatus includes: a brewing chamber including an inlet for heated water, an outlet for the brewed beverage, and an opening in communication with the opening of the capsule. A light source on the brewing apparatus emits light into the base via the light inlet surface of the capsule. The light conductor conducts the light to the light-output surface. A light detector of the brewing apparatus detects light emitted by light-output surface on the base of the capsule. A method of operating the brewing system and a capsule system are also described.

The present invention is directed to a Modular Liquid Infusing, Flavoring and Dispensing Device that provides a means to infuse flavor into liquids for variable periods of time prior to dispensing, and after the brewing process, wherein the system provides a means to control the rate at which the liquid is dispensed, reduces the trauma to the dispensed liquid, and reduces the amount of foaming in the dispensed liquid. The present invention further provides a method for using the Modular Liquid Infusing, Flavoring, and Dispensing Device.

The present invention is directed to recombinant thraustochytrids that grow on sucrose and cell cultures comprising the recombinant thraustochytrids as well as methods of producing cell cultures, biomasses, microbial oils, compositions, and biofuels using the recombinant thraustochytrids.

A hand operated gripping tool includes a first jaw unit having a first work piece engaging portion, a support member extending generally transversely with respect to the first jaw unit, a first handle at the second end of the support member, a second jaw unit having a second work piece engaging portion, and a second handle having an end portion pivotally attached at the second jaw unit. A guiding device is disposed at the end portion of the second handle. The guiding device has an engaging element and a biasing element, and the engaging element is biased or urged toward and into engagement with the second reaction surface by the biasing element. The engaging element engages the second reaction surface as the second jaw unit moves along the support member to adjust the size of the work piece receiving space.

An apparatus includes a spool configured to supply a wire, a cutting device configured to form a notch in the wire, and a capillary configured to bond the wire and to form a stud bump. The apparatus is further configured to pull the wire to break at the notch, with a tail region attached to the stud bump.

A surgical tool assembly includes a pair of opposing jaws. Further, a viewing opening may be provided in at least one of the opposing jaws. The viewing opening may extend from an upper to a lower surface of the opposing jaw in which the viewing opening is provided. The viewing opening may include a material retainer provided proximate the lower surface of the opposing jaw in which the viewing opening is provided. The material retainer may include an inclined surface inclined towards a central axis of the viewing opening. A grasping insert may be molded onto a lower surface of the opposing jaw in which the viewing opening is provided and an elastomeric material of the grasping inserts may within the viewing opening, the material of the grasping inserts covering the inclined surface of the first material retainer.

A method and tool for driving a bit. The tool includes a handle extending along a longitudinal axis between a first end and a second end. The handle can be in a first configuration to provide a first drive ration. In a second configuration, such as a T-shaped configuration, a gear assembly can be disengaged to provide a second drive ratio for the bit driving system.

Tools (100) are provided for use in uncapping one or more of a plurality of linearly-oriented, spaced-apart tubes; each cap having a cap upper surface with a depression. The tools comprise a body (30) having first portion (40) for engagement by a user and a second portion (50) for engaging a plurality of caps. The second portion comprises a plurality of spaced-apart projections (60). Each projection is configured for releasably engaging a cap. The projection may comprise two or more spaced-apart projection elements (62,64). Optionally, the first portion is configured in a non-coplanar relationship with respect to the second portion. Methods of use are also provided.

An apparatus for stitching an interior component is disclosed herein. The component having an outer skin layer and the apparatus is a single needle chain stitch machine with a rotary looper and wherein a needle of the apparatus descends through the interior component and a hook of the rotary looper engages a thread loop formed during retraction of the needle after it has descended through the interior component; and wherein the apparatus further includes a mechanism for moving the interior component relative to the needle and looper to establish a stitch length.

An apparatus includes a processor and a memory. The memory is configured to store computer-readable instructions that, when executed by the processor, instruct the processor to perform processes including acquiring pattern data, specifying an outline of the embroidery pattern based on the pattern data, creating hole data for causing the sewing machine to form a plurality of holes including one or more first holes and one or more second holes, creating first stitch data for causing the sewing machine to sew one or more stitches for the one or more first holes, and creating embroidery data for causing the sewing machine to form one or more first holes, and sew the one or more stitches for the one or more first holes, and causing the sewing machine to form the one or more second holes, before causing the sewing machine to sew an outline pattern.

A thread hook and a looper thread holder are arranged on a rear side of a needle drop position of a sewing machine. When usual sewing is completed, the thread hook and the looper thread holder swing and move close to a looper. A hook part provided at a tip end of the thread hook holds a needle thread loop caught by the looper and positions it on an advance end side of the looper away from the needle drop position, and a thread receiving part provided at a tip end of the looper thread holder holds a looper thread extending from the looper to cloths and positions it on the front side away from the needle drop position. The sewing machine performs sewing for at least one stitch while maintaining positions of the needle thread loop and the looper thread.

One example includes a body formed of body fabric, the body defining a body pocket opening, a body pocket disposed in an interior of the body and coupled to the body pocket opening and body plush disposed in the interior of the body, between the body pocket and the body fabric. The example includes a head formed of head fabric, the head having a posterior portion of the head coupled to the body at an anterior portion of the body, the head defining a head pocket opening disposed on an anterior portion of the head, a head pocket disposed in an interior of the head and coupled to the head pocket opening and head plush disposed in the interior of the head, between the head pocket and the head fabric. The example includes at least one pair of legs formed of leg fabric and fastened to the body.

A lower thread ending region detection apparatus prevents problems associated with false stitchings occurring from inability to detect lower thread's exhaustion during sewing operation. The lower thread ending region detection apparatus comprises: light control unit, which contacts a part of lower thread wound on a thread bobbin and activates or inactivates at least one of the functions of emitting light, reflecting light, passing light and blocking light, due to the effect of the physical movement force generated depending on whether the lower thread of the ending region is unwound; light receiving unit, which receives the light transferred out by the light control unit and outputs a detection signal; and control and notification unit, which analyzes the detection signal output from the light receiving unit to determine whether the lower thread has reached the ending region and outputs the result to the user.

An apparatus for thread-stitching a book block includes a thread tensioning device configured to store and tension a binding thread. A single actuator, including a servo drive, drives the thread tensioning device. The method includes storing a length of binding thread; in a separate step, tensioning the binding thread; and thread-stitching the book block.

A sewing direction control apparatus for sewing machine, comprising: a base plate, a circular ring-shaped transmission element dispose on the base plate and a driving element with a driving unit. During sewing, the driving unit drives the transmission element, rotating a sewing product placed at the center of the transmission element with the driving element, thereby controlling the sewing direction of the sewing product, and thus improving the sewing accuracy. The direction control apparatus has low cost, and is suitable for various types of automatic sewing machines.